title: Disrupting the oncogenic synergism between nucleolin and Ras results in cell growth inhibition and cell death.
abstract: BACKGROUND
  The ErbB receptors, Ras proteins and nucleolin are major contributors to malignant transformation. The pleiotropic protein nucleolin can bind to both Ras protein and ErbB receptors. Previously, we have demonstrated a crosstalk between Ras, nucleolin and the ErbB1 receptor. Activated Ras facilitates nucleolin interaction with ErbB1 and stabilizes ErbB1 levels. The three oncogenes synergistically facilitate anchorage independent growth and tumor growth in nude mice.
  
  
  RESULTS
  In the present study we used several cancer cell lines. The effect of Ras and nucleolin inhibition was determined using cell growth, cell death and cell motility assays. Protein expression was determined by immunohistochemistry. We found that inhibition of Ras and nucleolin reduces tumor cell growth, enhances cell death and inhibits anchorage independent growth. Our results reveal that the combined treatment affects Ras and nucleolin levels and localization. Our study also indicates that Salirasib (FTS, Ras inhibitor) reduces cell motility, which is not affected by the nucleolin inhibitor.
  
  
  CONCLUSIONS
  These results suggest that targeting both nucleolin and Ras may represent an additional avenue for inhibiting cancers driven by these oncogenes.
authors.affiliation: Department of Neurobiology, Tel-Aviv University, Ramat-Aviv, Israel.
authors.forename: Sari
authors.initials: S
authors.lastname: Schokoroy
authors.forename: Dolly
authors.initials: D
authors.lastname: Juster
authors.forename: Yoel
authors.initials: Y
authors.lastname: Kloog
authors.forename: Ronit
authors.initials: R
authors.lastname: Pinkas-Kramarski
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide; D063646:Carcinogenesis / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism*; D005204:Farnesol / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012459:Salicylates / Q000494:pharmacology; D018631:ras Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000097796:Nucleolin
chemical_list: D052157:Aptamers, Nucleotide; D066246:ErbB Receptors; D005204:Farnesol; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D012459:Salicylates; D018631:ras Proteins; D000097796:Nucleolin; C513936:AGRO 100; C093323:farnesylthiosalicylic acid